Department of Nutrition, University of California, Davis, Davis, CA 95616, USA.
Center on Aging, University of Connecticut Health Center, Farmington, CT 06030, USA.
Nutrients. 2023 Jun 8;15(12):2679. doi: 10.3390/nu15122679.
The endocannabinoid system (ECS) participates in regulating whole body energy balance. Overactivation of the ECS has been associated with the negative consequence of obesity and type 2 diabetes. Since activators of the ECS rely on lipid-derived ligands, an investigation was conducted to determine whether dietary PUFA could influence the ECS to affect glucose clearance by measuring metabolites of macronutrient metabolism. C57/blk6 mice were fed a control or DHA-enriched semi-purified diet for a period of 112 d. Plasma, skeletal muscle, and liver were collected after 56 d and 112 d of feeding the diets for metabolomics analysis. Key findings characterized a shift in glucose metabolism and greater catabolism of fatty acids in mice fed the DHA diet. Glucose use and promotion of fatty acids as substrate were found based on levels of metabolic pathway intermediates and altered metabolic changes related to pathway flux with DHA feeding. Greater levels of DHA-derived glycerol lipids were found subsequently leading to the decrease of arachidonate-derived endocannabinoids (eCB). Levels of 1- and 2-arachidonylglcerol eCB in muscle and liver were lower in the DHA diet group compared to controls. These findings demonstrate that DHA feeding in mice alters macronutrient metabolism and may restore ECS tone by lowering arachidonic acid derived eCB.
内源性大麻素系统 (ECS) 参与调节全身能量平衡。ECS 的过度激活与肥胖和 2 型糖尿病的负面后果有关。由于 ECS 的激活剂依赖于脂质衍生的配体，因此进行了一项研究，以确定膳食多不饱和脂肪酸 (PUFA) 是否可以通过测量宏量营养素代谢的代谢物来影响 ECS 以影响葡萄糖清除率。C57/blk6 小鼠喂食对照或富含 DHA 的半纯化饮食 112 天。在喂食这些饮食 56 天和 112 天后，收集血浆、骨骼肌和肝脏进行代谢组学分析。主要发现特征是喂养 DHA 饮食的小鼠的葡萄糖代谢发生转变，脂肪酸的分解代谢增加。根据代谢途径中间产物的水平以及与 DHA 喂养相关的途径通量的改变代谢变化，发现葡萄糖的利用和促进脂肪酸作为底物。随后发现更多的 DHA 衍生甘油脂质，导致花生四烯酸衍生的内源性大麻素 (eCB) 减少。肌肉和肝脏中 1- 和 2-花生四烯酰甘油 eCB 的水平在 DHA 饮食组中低于对照组。这些发现表明，DHA 喂养在小鼠中改变了宏量营养素代谢，并可能通过降低花生四烯酸衍生的 eCB 来恢复 ECS 张力。
